Synergistic effect of anti-envelope and anti-CD81 antibodies on inhibition of HCV infection.

HCVpp of strains P02VJ or HCVcc-Luc Jc1 were pre-incubated with anti-E2 mAb IGH461 or purified heterologous anti-HCV IgG (1 or 10 µg/ml) obtained from an unrelated chronically infected subject or isotype control IgG for 1 hour at 37°C and added to Huh7.5.1 cells pre-incubated with serial dilutions of anti-CD81 QV-6A8-F2-C4 or rat isotype control mAbs. HCVpp entry and HCVcc infection were analyzed by luciferase assay. The Combination Index (CI) was calculated as described [42], [43]. A CI less than 0.9, between 0.9 and 1.1, and more than 1.1 indicates synergy, additivity, and antagonism, respectively. CI for anti-CD81 mAb in combination with 10 µg/ml anti-HCV IgG in HCVpp entry inhibition was calculated for an IC75 as the combination resulted in an inhibition below the IC50 and is indicated by a star (*). IC50 of anti-envelope antibodies: anti-E2, 70±5 µg/ml (for HCVpp); anti-HCV IgG, 40±3 µg/ml (for HCVpp), 120±6 µg/ml (for HCVcc).